Abstract
C-reactive protein (CRP) is a significant contributor to atherosclerosis and a powerful predictor of cardiovascular risk. The role of CRP in endothelial cell (EC) activation has been extensively investigated, but the underlying mechanisms have not been fully elucidated. The effect of glycogen synthase kinase-3β (GSK-3β) on CRP-induced EC activation was evaluated in this study. We observed that CRP decreased endothelial nitric oxide synthase (eNOS) activity during EC activation. CRP also activated GSK-3β by dephosphorylating its Ser9 level and reducing β-catenin protein expression in a time-dependent manner. We also found that the GSK-3β inhibitors TDZD-8 and SB415286 partially restored eNOS activity and suppressed the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. These data provide new evidence for the involvement of GSK-3β in EC activation.
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Ferri, C., Croce, G., Cofini, V., De Berardinis, G., Grassi, D., Casale, R., Properzi, G., and Desideri, G. (2007) Curr. Pharm. Des., 13, 1631–1645.
Koenig, W. (2005) Int. J. Cardiol., 98, 199–206.
Paffen, E., and DeMaat, M. P. (2006) Cardiovasc. Res., 71, 30–39.
Danesh, J., and Pepys, M. B. (2009) Circulation, 120, 2036–2039.
Venugopal, S. K., Devaraj, S., Yuhanna, I., Shaul, P., and Jialal, I. (2002) Circulation, 106, 1439–1441.
Antonova, O. A., Loktionova, S. A., Romanov, Y. A., Shustova, O. N., Khachikian, M. V., and Mazurov, A. V. (2009) Biochemistry (Moscow), 74, 605–612.
D’Alessandris, C., Lauro, R., Presta, I., and Sesti, G. (2007) Diabetologia, 50, 840–849.
Nabata, A., Kuroki, M., Ueba, H., Hashimoto, S., Umemoto, T., Wada, H., Yasu, T., Saito, M., Momomura, S., and Kawakami, M. (2008) Atherosclerosis, 196, 129–135.
Tanigaki, K., Mineo, C., Yuhanna, I. S., Chambliss, K. L., Quon, M. J., Bonvini, E., and Shaul, P. W. (2009) Circ. Res., 104, 1275–1282.
Xu, J. W., Morita, I., Ikeda, K., Miki, T., and Yamori, Y. (2007) Mol. Endocrinol., 21, 564–573.
Ma, S., Liu, S., Huang, Q., Xie, B., Lai, B., Wang, C., Song, B., and Li, M. (2012) J. Biol. Chem., 287, 22521–22532.
Forde, J. E., and Dale, T. C. (2007) Cell Mol. Life Sci., 64, 1930–1944.
Grimes, C. A., and Jope, R. S. (2001) Prog. Neurobiol., 65, 391–426.
Krasilnikov, M. A. (2000) Biochemistry (Moscow), 65, 59–67.
Choi, S. E., Kang, Y., Jang, H. J., Shin, H. C., Kim, H. E., Kim, H. S., Kim, H. J., Kim, D. J., and Lee, K. W. J. (2007) Vasc. Res., 44, 365–374.
Ramirez, S. H., Fan, S., Zhang, M., Papugani, A., Reichenbach, N., Dykstra, H., Mercer, A. J., Tuma, R. F., and Persidsky, Y. (2010) Am. J. Pathol., 176, 881–892.
Choi, S. E., Jang, H. J., Kang, Y., Jung, J. G., Han, S. J., Kim, H. J., Kim, D. J., and Lee, K. W. (2010) Vasc. Pharmacol., 53, 264–272.
Eto, M., Kouroedov, A., Cosentino, F., and Luscher, T. F. (2005) Circulation, 112, 1316–1322.
Tsoyi, K., Jang, H. J., Nizamutdinova, I. T., Park, K., Kim, Y. M., Kim, H. J., Seo, H. G., Lee, J. H., and Chang, K. C. (2010) Atherosclerosis, 213, 115–121.
Cuzzocrea, S., Crisafulli, C., Mazzon, E., Esposito, E., Muia, C., Abdelrahman, M., Di Paola, R., and Thiemermann, C. (2006) Br. J. Pharmacol., 149, 687–702.
Gong, R., Rifai, A., and Dworkin, L. D. (2006) Kidney Int., 69, 1166–1174.
Beurel, E., Michalek, S. M., and Jope, R. S. (2009) Trends Immunol., 31, 24–31.
Martin, M., Rehani, K., Jope, R. S., and Michalek, S. M. (2005) Nat. Immunol., 6, 777–784.
Bowes, A. J., Khan, M. I., Shi, Y., Robertson, L., and Werstuck, G. H. (2009) Am. J. Pathol., 174, 330–342.
McAlpine, C. S., Bowes, A. J., Khan, M. I., Shi, Y., and Werstuck, G. H. (2011) Arterioscler. Thromb. Vasc. Biol., 32, 82–91.
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Published in Russian in Biokhimiya, 2013, Vol. 78, No. 8, pp. 1165–1170.
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Liu, SJ., Liu, WH., Zhong, Y. et al. Glycogen synthase kinase-3β is involved in C-reactive protein-induced endothelial cell activation. Biochemistry Moscow 78, 915–919 (2013). https://doi.org/10.1134/S0006297913080087
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DOI: https://doi.org/10.1134/S0006297913080087